Rat model of pulmonary arteriovenous malformations after right superior cavopulmonary anastomosis

Abstract

We developed a rat model of pulmonary arteriovenous malformations after cavopulmonary anastomosis. We sought to determine whether this model reproduces the angiographic and histologic features seen in the human condition. Eight Sprague-Dawley rats underwent a right superior cavopulmonary anastomosis with the use of microsurgical techniques. Between 2 and 13 mo, pulmonary angiography was performed, the animals were euthanized, and the lungs were removed. Microscopic sections of the lung were stained with an endothelial-specific antibody (von Willebrand factor). Microvessel density was determined by counting vessels staining positively for von Willebrand factor, and the shunted and nonshunted (control) lungs were compared for each animal. Pulmonary angiography revealed time-dependent development of arteriovenous malformations. Microvessel density demonstrated a time-dependent increase in the shunted lung compared with the control lung (simple linear regression of the ratio of the microvessel density of the shunted lung divided by the microvessel density of the control lung on time; R(2) = 0.79, P = 0.003). This animal model reproduces the same angiographic and microscopic features of pulmonary arteriovenous malformations that develop in humans after cavopulmonary anastomosis. This appears to be a valid model that may be used to further study etiologic mechanisms for this phenomenon.